New Surgical Options for Treatment of Canine Osteosarcoma
ACVIM 2008
James P. Farese, DVM, DACVS
Gainesville, FL, USA

Introduction

Osteosarcoma is the most common primary bone tumor affecting dogs. Lesions typically involve the metaphyseal region of the distal radius, proximal humerus, distal or proximal femur and distal or proximal tibia. In most instances both osteoproductive and osteolytic processes are occurring simultaneously. The tumors typically arise from within the bone; however, once cortical bone destruction occurs, portions of the tumor extend outside the bone causing periosteal response and extracortical soft tissue swelling as well. When lesions are left untreated, severe pain and eventually pathologic fracture may occur.

The most commonly recommended treatments for canine appendicular osteosarcoma include medical management (alleviation of associated bone pain), amputation (+/- chemotherapy), limb-sparing surgery and chemotherapy, radiation therapy (fractionated radiation therapy and stereotactic radiosurgery (SRS)).

Surgery

Amputation

Amputation remains the "gold standard" form of treatment for appendicular osteosarcoma. Advantages include complete tumor removal with almost no chance of recurrence, elimination of pain associated with the tumor, low rate of complications and relatively low cost. Guidelines are as follows:

Tumor location

Amputation level

Distal radius

Proximal to scapula (or mid-humeral)

Proximal humerus

Proximal to scapula

Distal tibia

Mid-femoral or coxofemoral disarticulation

Proximal tibia

Same as for distal tibia

Distal femur

Coxofemoral disarticulation

Proximal femur

Partial pelvectomy or coxofemoral disarticulation*

* Depending on extent of involvement

Although amputation has become the most common form of therapy, many dogs are not considered suitable candidates for amputation due to concurrent orthopedic or neurological conditions. There is growing interest among owners of dogs affected with osteosarcoma for alternatives to surgery.

Limb-Sparing Surgery

Limb-sparing is most commonly performed on tumors affecting the distal radius. This involves performing an osteotomy in the central area of the radial diaphysis, excising the tumor and associated bone by dissecting around the tumor pseudocapsule, filling the resulting bone defect with some weight-supporting material and spanning the entire length of the radius, implant and carpal joint with a limb-sparing bone plate. Materials that have used thus far include cortical allografts, cement spacers (PMMA), autoclaved autogenous bone, pasteurized autogenous bone, and a metal radial endoprosthesis (available through VOI--Veterinary Orthopedic Implants). Another technique utilizes the phenomenon of distraction osteogenesis to fill the bone defect. With this technique a segment of bone is cut from the remaining bone end and is "transported" (bone transport osteogenesis--BTO) across the defect via circular external skeletal fixation (i.e., Ilizarov). There have been some reports of other anatomic locations being treated (e.g., proximal humerus, distal tibia); however, only the distal radius location is routinely performed as complications such as implant failure and poor limb function are common when surgical limb-sparing techniques are used to treat tumors affecting the humerus, femur, and tibia. Cost of limb-sparing is very high (ranging from $8,000-12,000 with chemotherapy).

We (at the University of Florida) are also in the early stages of development of another bone transport osteogenesis technique that involves transverse transport of a portion of the adjacent ulna into the radial defect.1 Potential benefit of this procedure over conventional bone transport is that the distraction time (and therefore the time to fixator removal) is significantly shorter. However, clinical evaluation of this technique is only in the early stages.

Prior to performing limb amputation or limb-sparing surgery it is best to do a bone scan to make sure there is no evidence of occult skeletal metastasis or a synchronous primary tumor.

Metastasectomy

Pulmonary metastasectomy may be effective in some cases.2 In rare instances, removal of 1-2 pulmonary metastatic nodules can result in additional long-term control. An example would be a dog that was treated with amputation and chemotherapy that developed a slow growing solitary pulmonary nodule some time later (e.g., 2 years post-op). It is important to make sure multiple lesions are not present (i.e., 3 or more nodules) and CT scan of the lungs can help confirm this. It is not known how well dogs that present with a single pulmonary nodule at the time of the initial diagnosis would do with metastasectomy and treatment of the primary tumor. This is an interesting population that deserves more study; however, most pet owners are usually reluctant to elect such a treatment course given the poor prognosis.

Radiation Therapy

Osteosarcoma was previously thought to be a radiation-resistant tumor. However, recent reports indicate that radiation can be an effective method for palliation of pain and some degree of local control, especially when combined with chemotherapy. The effective palliative radiation dose has ranged from 3-22 Gy given in multiple fractions. Such fractionated therapy requires multiple anesthetic episodes and repeated or prolonged hospitalization, which may preclude the feasibility of treatment.

Recently a report was published on curative intent fractionated therapy. In this report only 1/3 of the cases did not experience progression of the primary tumor and the median survival time was @ 7 months. However, several of the tumors were completely controlled by the treatment and had 100% necrosis of the tumor at necropsy. It appears that some tumors respond better than others but there is still no way to predict which will respond well prior to therapy.

A form of intra-operative radiation therapy is also being evaluated at Colorado State University. This procedure, called the "flip and nuke", involves osteotomizing the affected bone in an area not affected by tumor, "flipping" or lifting the affected portion of the bone out of the wound (joint attachments maintained) and irradiating the tumor with a single dose of 70 Gy ("nuking") with a linear accelerator. A 1 cm long portion of the bone at the level of the osteotomy is collimated out of the field to maintain cellular activity and facilitate healing of the osteotomy. A bone plate is typically used to stabilize the osteotomy for healing and the intramedullary portion of the bone is usually filled with cement to increase strength. This technique has been used to successfully treat osteosarcoma of the distal radius, proximal humerus, distal femur and tibia. Complications include pathologic fracture and implant associated infection.

An injectable form of radiation therapy is also under investigation. This involves a single systemic injection of a radionuclide (samarium-153-EDTMP) that preferentially seeks bone (linked to a bisphosphonate). Preliminary evaluation shows potential for the temporary alleviation of pain; however, disease progression is not prevented and, thus far, the survival time appears to be @ 4-6 months. Isolated limb perfusion with samarium and other radionuclides is being evaluated at CSU to see if higher tissue levels can improve local tumor control.

Stereotactic radiosurgery (SRS) involves the delivery of a single, high dose of radiation in a highly targeted manner while sparing the surrounding tissues.3 Theoretically, a single dose of radiation has a greater biologic effect than an equivalent total dose given in fractions (e.g., single dose of 30 Gy vs. 3 treatments of 10 Gy). Since a single high dose will also cause more late effects in the surrounding tissues it is important that the dose distribution accurately conforms to the tumor "target". We are presently treating with a combination of radiosurgery and chemotherapy (carboplatin 300 mg/m2 at the time of therapy then follow-up chemotherapy with carboplatin, doxorubicin or an alternating combination of the two). To perform SRS, a targeting array must be temporarily (overnight) and rigidly fixed to the affected bone. This is usually done with two 1.5mm diameter pins and casting material. SRS for osteosarcoma is performed with 30 Gy prescribed to the 75% isodose line, so the center of the tumor receives @ 40 Gy.

Subjective evaluation of tumoral swelling and lameness has shown improvement in all cases treated, usually within three weeks. Our preliminary data indicate that the combination of coverage of the tumor with 30 Gy and chemotherapy consistently provide long-term tumor control and likely complete tumor kill. Overall median survival time in the initial eleven dogs treated was 363 days (range 145-763).

We are also starting to use SRS to treat tumors in upper extremity locations. The limiting factors of SRS therapy for appendicular osteosarcoma are the size of the tumor and the condition of the bone at the time of therapy, as adequate coverage of large tumors with the 3,000 cGy isodose line is not always possible and the risk of pathologic fracture remains after treatment. Thus, SRS should ideally be used to treat appendicular osteosarcomas that are relatively small and have caused minimal bone destruction. Cost is similar to that of limb-sparing surgery.

References

1.  Jehn C, et al. Vet Surg 2007;36(4):324.

2.  Obrien M, et al. Vet Surg 1993;22(2):105-.

3.  Farese JP, et al. J Am Vet Med Assoc. 2004;225(10):1567,1548.

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

James Farese, DVM, DACVS
University of Florida
Gainesville, FL


SAID=27